The objective of this proposal is to explain the mechanisms by which alcohol alters metabolism (with emphasis on carbohydrate), particularly as related to hormonal interactions and active membrane transport. Model systems of gastric mucosa, intestine, pancreas and liver will be used in which multiple parameters can be examined: (1) gastric mucosa-isolated gastric mucosa (using flux chamber) and intact perfused gastric mucosa (acute and chronic); (2) intestine-isolated intestine and intact perfused intestine (acute and chronic); (3) pancreas-isolated perfused pancreas, islet cell preparation, and intact perfused pancreas; (4) liver-isolated perfused liver, hepatocyte preparation, homogenates and intact liver (acute and chronic). Measurements will include electrophysiological methods (potential difference and resistance), unidirectional and net flux studies (Na+, Cl-, glucose and L-alanine), and biochemical determinations of carbohydrate intermediates--ATP, ADP, adenylyl cyclase, phosphodiesterase, glucose, glucagon, insulin, secretn, and ethanol.